Monday, October 31, 2016

Recently, Sarah Kopac and Jonathan Klassen described a new
model to understand the evolution of host-microbe symbioses in their paper “Can They Make It on Their Own? Hosts, Microbes, and the Holobiont Niche”.
In this model, hosts and microbes can change the shape of their respective
niches, and thereby the context in which selection can act. This permits a test of holobiont theory by identifying instances where an organism’s
phenotype depends on its symbiotic partners. Jonathan answered the following
questions, incorporating feedback from Sarah. Be sure to read all the way through.

1.What motivated the theory reported in
the paper?

It feels a bit murky now, but looking
back I think there were three main motivations. First, we were quite struck by
how host-microbe relationships can be thought of as a community ecology
problem, i.e., where and how do interspecific relationships form and what is
their outcome? So because much of the holobiont/hologenome literature has
started from a population-genetics perspective (e.g., http://journal.frontiersin.org/article/10.3389/fmicb.2014.00046/full),
we thought that drawing from a different intellectual tradition might be a way
to get beyond current sticking points in the field's discussion. Another interesting aspect of the community ecology
perspective is that it defines the context in which selection might act, leaving whether or not
selection does act as a separate
question. I think that it is too common to assume selection without rigorously
testing against alternative hypotheses, e.g., drift or dispersal limitation, to
our detriment. Second, we wanted to strongly highlight how any selection that
did occur likely impacted hosts and microbes differently, e.g., because
microbes have shorter lifespans and higher population sizes and dispersal rates
than their hosts (http://doi.wiley.com/10.1002/bies.201500074).
Third, one major take-away from my years of reading the lovely Dynamic Ecology
blog (https://dynamicecology.wordpress.com/)
is that mathematical models have a rigor and testability that verbal models
cannot match, and thereby overcome the potential for verbal models to become
misconstrued. Expressing our ideas mathematically so that they would be
unambiguously testable therefore became an important goal.

2.How did you come up with the title?

Truthfully, this was a revision suggested by one of the
reviewers. (And they were right - thanks!) Sarah came up with this version, and
I think it’s great because it really captures the key question of our model: do
host-microbe interactions matter for the evolution of either partner? I think
the answer is that it depends on the context, i.e., does the interaction change
the shape of either partner’s niche in a way that changes how selection might
act? I also love how (in my mind at least) there’s a U2 reference - https://www.youtube.com/watch?v=CuDqHtAR6L8.
I’ve long been a fan.

3.When and how did you two come together and
agree on this paper? Were there varied opinions about how to approach the
problem?

We agreed on the central idea of explaining holobionts in
terms of niche theory early on, and so were unified on that front. There was a
bit of divide and conquer after that, with Sarah focusing more on the examples
of different niche shifts and I focusing more on the models themselves. Then we came back together and made sure that
the examples we saw in the literature could be explained using our models.
I found it very helpful to get someone else’s view of the literature –
accurately synthesizing everything that’s out there alone would have been a
massive challenge.

4.What are the
most salient findings?

I think that it is striking how our models are agnostic
towards any particular mechanism of host-microbe interaction. For example, a
similar shift in a host’s niche could be result from that host selecting
microbes with a particular trait from the environment each generation, or it
could be due to tight host-microbe co-evolution and vertical transmission. The
important thing is that in either case the interaction changes the shape of a
host’s niche in a way that selection might act upon. Both partners are
therefore needed to completely describe host evolution. I am also struck by how
our models accommodate the full diversity of symbiotic relationships, including
the various forms of conflict that change the shape of a host’s niche but in a
different way than mutualism. Finally, it seems that the symbiosis community
has already been at least implicitly thinking in terms of our model because it
was easy to find studies that had already tested it by changing one parameter
at a time, e.g., by swapping microbiomes between constant host genotypes and
vice versa. Hopefully our work can guide future experiments that continue to
explicitly test these ideas.

5.What are the
most crucial questions moving forward in your mind? What do you want
to do next?

Perhaps one problem with our model is that precisely
defining the shape of an organism’s niche is fiendishly difficult, mostly
because there are a potentially infinite number of niche axes to consider. I
think it will be interesting to understand how many of these are actually
needed to come up with an accurate niche description. For example, to what
extent to do microbe-microbe interactions need to be considered to describe how
microbes alter a host’s niche? I also think it will be critical to learn more
about microbes in non-host environments so that we can determine if hosts
modify the niches of their microbial symbionts outside of obvious cases like
intracellular mutualists and pathogens. Lastly and as described above, I think
it will be crucial to explicitly test whether any host-microbe interaction
phenotype actually arises due to selection, e.g., vs drift or dispersal
limitation.

6.Anything else
you want to add?

Thanks to our colleagues in the symbiosis field for being so
collegial, even in disagreement! I look forward to increasing the rigor of our
studies, and to a deeper understanding of how ecology and evolution both shape
host-microbe relationships.

Wednesday, October 19, 2016

I returned last month from Kiel University for the 109th German Zoological Society Meeting. A Zoological Society Meeting alone is impressive these days, not to mention its 109 year history. Thomas Bosch invited me out for the keynote lecture. Thomas has been at the forefront of advancing a better appreciation of the natural world, namely the intricate interactions between a simple model system of the non-senescent cnidarian Hydra and its microbial community. Hydra represent an early key transition in the evolution of animals and therefore are critical to studying the origins of developmental mechanisms. Thomas is a CIFAR fellow and directs the Metaorganisms Collaborative Research Center, which is a beacon for systems biology thinking about the animal-microbiome assemblage.

Anyway, I presented our long-term studies on the role of bacteria in reproductive isolation and the origin of species. I presented old and new work, most recently by @ABrooksy19, @KevinDKohl, @liveinsymbiosis and @teddy1387 on phylosymbiosis across various animals. This work is currently in press. Here's the talk and interview that the Collaborative Research Center clearly put a lot of work into - many thanks to the team.

Saturday, October 15, 2016

The latest craze over phage WO, the bacterial virus that
infects Wolbachia, has been both
exciting and overwhelming. The press is great at communicating the science in a digestible
format, but it can sometimes become sensationalized and misleading. When one
press release builds upon the hype of a previous release, the end result is
much like the game of telephone. As an author of “Eukaryotic association module in phage
WO genomes from Wolbachia”, I want to
make sure that the science in the public's eye is not over-represented and that we are providing a
realistic view of the data.

Let’s first talk about what the paper is not, though headlines have claimed otherwise.

·Phage WO
does not encode the entire black widow venom (latrotoxin) gene. In fact, as
we present in the paper, it contains DNA that is similar to just the C-terminal
domain. This particular region of the gene is associated with the protoxin that
is hypothesized to be involved in lysis of the spider’s secretion cells.

·The phage
did not necessarily “steal” the DNA from the spider. Yes, viruses hijack
DNA from their hosts and this has been shown in both bacterial viruses and
animal viruses. Viruses are incredible, rapidly evolving entities. Due to the
level of divergence between the sequences in this particular study, the genetic
transfer, if it did happen, occurred long, long ago. We can’t definitively say
if the spider transferred to phage or phage to spider, but in our opinion both
would be equally exciting. The current data leans towards spider to virus,
possibly via a yet-to-be-discovered intermediary (see the paper for more
discussion). We also can’t definitively say that it was even a legitimate transfer
event. It could have been the result of convergent evolution. This is when
different organisms independently evolve similar traits. Given the fact that
widow spiders are often infected with Wolbachia,
and Wolbachia are often infected with
phage WO, there is an ecological niche that would provide opportunity for
genetic transfer. Plus, we present other examples in the paper that support genetic
transfer from animal to virus. Beyond that, many other research groups have
reported the transfer of DNA between Wolbachia
and their animal hosts, so the transfer between the phages and the animal is
not a huge stretch.

With that said, this is what the paper is:

·To our knowledge, this is the first report of animal-like DNA found in a bacterial virus.
Is this a completely absurd, mind-blowing discovery? Not really. Bacterial
viruses are known to exchange DNA with their bacterial hosts and animal viruses
with animals. However, we don’t really know much about how viruses of bacteria
might interact with animals. This field is really in its infancy.

·Phage WO
harbors a eukaryotic association module. About half of WO’s genome is
devoted to structural genes (such as capsid, tail, baseplate) and other common
phage elements. However, it also devotes a large percentage of its genome to
unique genes that putatively encode functions relevant to animal interaction. Like
some other viruses, phage WO appears to take different chunks of DNA from
different sources and mix and match the chunks to create unique genes. What do
these genes do? Do they retain the same functions as they did in the original
donor? These are all still mysteries to be solved; so many questions left to be
answered! I can tell you that some of the genes in the eukaryotic association
module quickly grabbed our attention and we look forward to expanding the story
of phage WO and Wolbachia in the
months to come. Stay tuned…

·Phage WO
integrates into the Wolbachia genome
via specific attachment (att) sites.
Why does this matter? Wolbachia is an
obligate intracellular endosymbiont. That means, it is dependent on its animal
host for survival and cannot be cultured outside of the animal cell (as you
would with standard free-living microbes such as E. coli). This makes it very hard for scientists to test functions
of specific genes and fully understand its biology. We are particularly
interested in Wolbachia because it
infects over 40% of all arthropods as well as some nematodes of human health
relevance and crustaceans. The identification of WO’s att sites offers a potential method of accessing the Wolbachia chromosome in order to unlock
its secrets. Using the phage may or may not work, but it’s the best chance we
have to-date.

On a personal note, I want to thank journalists such as Ed
Yong (The Atlantic - link) and Jacqueline Howard (CNN - link) for directly reaching out to
us, the scientists, and making sure that they understood the complexity of the
system rather than simply promoting catchy phrases. When it comes to science,
words matter. I agree that this is a fun system to explore, but I hope that the
science can stand on its own without adding falsehoods and making incorrect
conclusions.

Please don’t hesitate to reach out to scientists (including
me) if you have questions about our research and possibly don’t believe or
understand what you read in the news. We are honored to share this journey with
you and are particularly delighted to hear from the next generation of
researchers. Viruses are incredibly fascinating and, in my opinion, phage WO
tops the charts. We are just beginning to explore the landscape of viruses
infecting intracellular bacteria and I can’t wait to see what comes next.

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Biography

Seth
Bordenstein, Ph.D., is a biologist in the Departments of Biological
Sciences and Pathology, Microbiology, and Immunology at Vanderbilt
University (lab website) and the founding director of the Vanderbilt Microbiome
Initiative and worldwide science education program Discover the Microbes
Within! The Wolbachia Project (website, facebook). His laboratory studies the functional,
evolutionary and genetic principles that shape symbiotic interactions
between animals, microbes, and viruses as well as the major consequences
and applications of these symbioses to humans. The lab employs
hypothesis-driven approaches to study intimate (between hosts and
obligate intracellular bacteria) symbioses that deeply impact animal
reproduction and vector control as well as facultative (between
free-living organisms) symbioses that shape genome and species evolution
across the tree of life. Since animals regularly thwart or embrace the
microscopic world in both intimate and facultative symbioses, the
evolutionary history of animals is generally impacted by microbial
ecology. Bordenstein’s research and science education activities have
been highlighted in various popular science media including a
documentary on bacterial symbiosis, the New York Times, National
Geographic, Discover Magazine, Public Broadcasting Service, Scientific
American, and BBC Radio.